Tuesday, May 18, 2010

A Code That Isn't Universal

The DNA code, which translates DNA sequences into protein sequences, has always been claimed as extremely compelling evidence for evolution. The code was first described in the mid twentieth century and, among other things, was found to be universal, or nearly so. The same DNA code is used in the cells in your brain and your big toe. The same DNA code is used in different species. The same DNA code is even used across the major kingdoms. All tissues, all species use the same code? Surely they were not independently created—they must have evolved. And if the code varied, on the other hand, evolution would surely be falsified. In one fell swoop, the DNA code not only is another compelling evidence for evolution, it also demonstrates that evolution is falsifiable, a badge that is crucial for evolutionists who seek to distinguish themselves from those religious rascals. But now a new code has been discovered and, believe it or not, it is not universal.

Most people understand that genes are sections of DNA that code for molecular machines such as proteins. But what is less familiar is that in higher organisms many of the genes are broken up into expressed regions, or exons, which are separated by intervening regions, or introns. After the gene is copied the transcript is edited, splicing out the introns and glueing together the exons. Not only is it a fantastically complex process, it also adds tremendous versatility to how genes are used. A given gene may be spliced into alternate sets of exons, resulting in different protein machines. There are three genes, for example, that generate over 3,000 different spliced products to help control the neuron designs of the brain.

But how does the splicing machinery know where to cut and paste? The answer is that there is an elaborate code that exciting new research is helping to elucidate. The new massive study systematically analyzed how genes are alternatively spliced in four different types of mouse tissue: central nervous system tissue, muscle tissue, digestive system tissue, and whole embryos.

The study found significant signals that the splicing machinery seem to use to decide how to do its splicing. This splicing code is extremely complicated, using not only sequence patterns in the DNA transcript, but also the shape of transcript, as well as other factors.

What is also complex about the new code is that it varies substantially across the four tissue types. There is still much to learn, but there certainly is no question that this is no universal code. Is evolution still falsifiable?

Evolution is directly observed, including natural selection and sources of genetic variation. The evidence for the Theory of Common Descent is strongly supported, and known evolutionary mechanisms are sufficiently robust to explain historical transitions. Indeed, measured rates of evolution are much faster than required to explain the historical record.

In the context of the paper, Deciphering the splicing code, a 'code' is assembled by extracting RNA features resulting in a more predictive set of relationships than previous, simpler splicing codes. Modern models of network evolution predict a hierarchy of interactions, the precise details being a subject of active investigation. The paper shows how small mutations can result in significant evolutionary change, so the results support evolutionary theory.

"Evolution is directly observed, including natural selection and sources of genetic variation. The evidence for the Theory of Common Descent is strongly supported, and known evolutionary mechanisms are sufficiently robust to explain historical transitions. Indeed, measured rates of evolution are much faster than required to explain the historical record.

In the context of the paper, Deciphering the splicing code, a 'code' is assembled by extracting RNA features resulting in a more predictive set of relationships than previous, simpler splicing codes. Modern models of network evolution predict a hierarchy of interactions, the precise details being a subject of active investigation. The paper shows how small mutations can result in significant evolutionary change, so the results support evolutionary theory."

The headline of Dr Hunter's post is misleading. The story in the referenced paper is not about a "code" within the genetic code. It's about splicing signals.

The genetic code describes relationships between nucleotide triplet sequences and amino acid sequences at the level of translation on ribosomes. The "code" described in the referenced paper operates at the level of transcription of messenger RNA from DNA.

To conflate the two processes is a serious misunderstanding.

Dr Hunter:

There is still much to learn, but there certainly is no question that this is no universal code.

Of course it's not a universal code. It would otherwise be useless as process for differential gene expression in different tissues at different phases in development and in response to environmental changes.

Compare transcription factors as differential regulators of gene expression at another level in the process of messenger RNA synthesis:

Zachriel: Modern models of network evolution predict a hierarchy of interactions ...

Blas: maybe if you repeat it enough time will became truth.

Not an argument. The result appears consistent with evolutionary theory. Perhaps you could explain why it's not.

David: The "code" described in the referenced paper operates at the level of transcription of messenger RNA from DNA.

Note David's use of scare-quotes — just as the authors used in the abstract, "Here we describe the assembly of a ‘splicing code’, which uses combinations of hundreds of RNA features to predict tissue-dependent changes in alternative splicing for thousands of exons."

Alternative splicing has been known since the 1970's, and this isn't the first code developed.

These same references were posted at Telic Thoughts, but they apply here, as well. The 'splicing code' is consistent with and guided by evolutionary theory. Small mutational changes lead to novelty while maintaining proteomic integrity.

Cornelius,THis is exciting new research, but it appears that they use "contrastive" (your term) statistical inference, and therefore by your standards is "junk science." If you disagree, please explain why statistical inference is acceptable in this case but not in, for example, the Theobald study.

Cornelius,Reading further, I see that they actually use a competing models method in which they compare their results to those expected from an outlier noise model.

From the supplemental materials :"Some % inclusion values are expected to be outliers due to excessive noise and we often haveprior knowledge about which measurements may be attributed to experimental noise (e.g., due to lowgene expression). Our model therefore also has a competing outlier noise model."

and guess what? when their model beats the outlier noise model, they say that the results of their model are supported! truly "junk science", huh? I expect a new blog post about this metaphysical woo soon.

How did you detect design (or lack of evolution) in this system? How did you rule out competitive hypotheses? Please show references or calculations.

I'm also not sure how you can imply a universal splicing 'code' was an evolutionary prediction. Most prokaryotes lack introns entirely, and those that have them use them to produce unique products across time and tissue.

Secondly, that the Universal Genetic Code is near-universal is a better demonstration of evolution. Common origin, common machinery, slight adaptations and alterations through the history of life that correlate with phylogeny.

======The headline of Dr Hunter's post is misleading. The story in the referenced paper is not about a "code" within the genetic code. It's about splicing signals.======

Good point David. Succint, intriguing headlines are not always easy to come up with. Change made.

====Of course it's not a universal code. It would otherwise be useless as process for differential gene expression in different tissues at different phases in development and in response to environmental changes.====

Cornelius,it's about more than the title. the entire post is about the universal genetic code (evidence for UCD), which you claim is falsified by alternative splicing. But, as David pointed out, they are two entirely different things. Perhaps you should retract this post as well?

I would even argue the splicing 'code' is universal in metazoans. It isn't scattershot-the core machinery,* and a large number of junctions are conserved, but differentially REGULATED by a variety of inputs. Hence the 'code' in this paper.

*Features of spliceosome evolution and function inferred from an analysis of the information at human splice siteshttp://www.ncbi.nlm.nih.gov/pubmed/1474582

Dr. Hunters argument is somewhat akin to saying transcription factors can't have evolved because they don't act universally in all tissues, at all stages of development.

Totally bizarre interpretation of 'universal'.

Add the right transcript and splicing factors or signal to any metazoan, and you'll likely get the desired product, because the splicing machinery, junctions, and such tend to be conserved. Adding regulatory factors alters splicing in a time and tissue dependent manner.

But these signals are interpretable-this is how we can study splicing of human transcripts in model organisms (including yeast*). This has been incredibly important for understanding diseases of splicing-which might be the largest component of hereditary disease*2!

I disagree with Mr. Hunter in saying that a universal genetic code is evidence for evolution or common descent. It could just as easily be taken as evidence for a common designer. Why reinvent the wheel when it works so well? And creationists do no believe that each individual species was individually created. That is just a straw man that evolutionists to try and make creationists look and sound stupid. The original kinds were created separately, but within their genes, there was sufficient variety of information that all of the species we see today could have devolved from them - mostly through genetic drift and loss of genetic information. Creationists believe in evolution within the original kinds, but not in universal common ancestry where all life evolved from one original cell. This view makes much more sense than the evolutionary view. The near universal genetic code makes just as much sense under this view as it does in the evolutionary worldview. No, I take that back. It makes more sense because you have codes and information coming from intelligence rather than from pure chance which has no evidence and requires countless miracles of chance to happen.

"The original kinds were created separately, but within their genes, there was sufficient variety of information that all of the species we see today could have devolved from them - mostly through genetic drift and loss of genetic information."

Can you give some more informations on how many kinds were created? When?

====it's about more than the title. the entire post is about the universal genetic code (evidence for UCD), which you claim is falsified by alternative splicing.====

No, I didn't claim the genetic code claim is falsified by the splicing code. But what we do know is that evolution must have created an extremely complex code specifying how eukaryotic mRNA is to be spliced. And this code is tissue-specific, so evolution must have created all these different codes. Do you think evolution did that?

In the face of evidence to the contrary*, you present what you think. What data to the contrary, what calculation, what falsification do you have that this process is unevolved? Science isn't about how you feel about a process, Dr. Hunter.

"So the designer would design biology so as to make it look like it evolved?"

Isn't that becoming the only reasonable hypothesis? Either that or deny the data. If humans are an independent creation, why do we share machinery, splice junctions, etc. that differ in a precisely in a way that makes us look like we share common ancestry with all life? Heck, Creationists were proposing precisely that as THE alternative on the Douglass Theobald blog thread.

Another one liner to the least consequential part of my post. Care to answer any of the rest or how you detected design and ruled out evolution in this or any other system?

Or is this another gee-whiz, therefore vague allusion to some alternative you won't actually advocate.

And anyway, I do feel this was an accurate restatement of your argument. You don't feel like this system evolved. That is all. No calculation, no data. No hint of empiricism, however moderated you like it.

Me, quoting you:

"And this code is tissue-specific, so evolution must have created all these different codes. Do you think evolution did that? "

"So the designer would design biology so as to make it look like it evolved? "

For all we know about DNA, how much do you think we really understand? I think of geneticists as analogous to aborigines with no mechanical knowledge and that have never seen an aircraft of any sort examining a grounded helicopter and speculating on how it might work. Do you think that is a fair comparison?

Sounds like a difficult question. I will say that we do have quite impressive knowledge of genetics, etc. But yes, it often seems like there is much more of the onion to peel back. Where exactly we are is hard to say, but I wouldn't say we can't at least stand back and make some meaningful observations.

=====I disagree with Mr. Hunter in saying that a universal genetic code is evidence for evolution or common descent. It could just as easily be taken as evidence for a common designer.=====

So the designer would design biology so as to make it look like it evolved?

=====

A common DNA code system has only a relationship to evolutionary hypothesis through the fact that it might fit / support a common descent of bio-information. In a random environment the chances of a code system to remain unchanged for this long period is very small. That poses problems for the mechanism of the evolutionary progress because it has to assume the code system to be completely immutable and on what basis will that claim be maid? It's irrelevant to claim the optimum nature of the DNA code system or the nature of the medium that carries the messages, to be the reason that it is universal and unchanged over the entire evolutionary time scale. Nature has many ways / candidates for capturing code systems like binary systems that can be captured in molecular media (Just think of what the IT industry uses today). We all know that a binary media can be used to build various other code systems.

Back to the DNA code system. The claim that it proofs evolution is not consistent with the process of evolution but only based on an unfounded assumption of the state of affairs that can be expected, should the "Tree of common descent" is true. However if a mechanism for this state of affairs has to be chosen then the act of intelligence becomes the best documented candidate.

Think of it in this way. We are trying to create AI systems using various kinds of codes and media to store those codes. What prevents nature from doing the same. If Darwinist mechanisms were at work in nature then we should expect at least the same kind of "trail code systems". Positing a single "funnel & hose" through which the bio-code could have came into existence does not sound random at all.

In this sense the existence of any other code systems instantiated on any other physical media should be a proof that the DNA code system is not the only way to bringing bio-info to living systems. Just think how many living systems is possible - Star Trek on steroids.

That's not the case for the proposed naturalistic processes. Why talk about consciousness and thought as something non-naturalistic, if you are a naturalist / materialist?

Personally I think that there is nothing in nature that can cause a code, a message, consciousness, a mind, thought because it always presuppose something that can and want and to convey meaning. Nature is just not doing that, our consciousness does, as far as we know (Hurbert Yockey's work might be insightful on this matter). What ever else has self awareness needs philosophy to find the best answer.

However Darwinist thinking has to suppose nature did all of these and one day AI as well. Therefore the comparison has to stand in a naturalistic world view.

There is no physical reason that I should trust my body (brain) to contain or constitute my consciousness. However it certainly constitute a physical instantiation of my consciousness. Hence the message I write in the code you can decipher most probably has no physical origin even though all my physical faculties played a part in getting the message across. (Alvin Plantinga has some great thoughts against naturalism that would help clarify this view - it is part of the commonly held dualistic view of reality)

Michael says: "In a random environment the chances of a code system to remain unchanged for this long period is very small."

Is it? What is that chance, and why is it very small? I wonder, because the opposite of this strawman is plainly true. If the code is changed (reassigning a tRNA), it has the cascading effect of altering every amino acid in every protein using that codon. In a metazoan, the odds that this will produce a viable individual are vanishingly small. Do you actually think that such a reassignment would be a small change that would not be subject to selection?

I strongly suggest you read some of the literature on codon reassignment - of which there is a reasonably large base - before casually making unsubstantiated statistical claims.

"That poses problems for the mechanism of the evolutionary progress because it has to assume the code system to be completely immutable and on what basis will that claim be maid?"

The code system is not immutable, and that claim is not made by any evolutionary geneticists. The code system is subject to mutation and strong selection, as evidenced by the minor differences in the mitochondrial genetic codes. Incidentally, it is the relatively high and biased mutation rate that mtDNA is subject to that is likely to be responsible for this. Again, see the literature for some interesting discussions on this e.g. Osawa and Jukes (1989).

You contradict yourself to such an extent that you should get a chance to try again...

I am very aware of the fact that it will be catastrophic for the DNA code system to change at all during the entire proposed evolutionary period. That is my argument exactly. Your objection on the one hand shows this but on the other hand you don't show me how Darwinian processes will prevent the DNA code to change at all. That is my argument, Darwinian processes will most probably change the DNA code system, not the straw man you erected.

Then comes the fantastic part when you end by saying the DNA code system IS subject to mutation and selection. Either you don't know the difference between a code system and the messages it is used for to represent, or you support my point that there is nothing to prevent mutation to alter the actual code system and not just the messages written in that code system.

Hope this will help you to see your self contradicting position. But in the end you supported my argument so strongly that I have to say thank you very much.

Is my understanding wrong, if I read in this post that:* The DNA code is universal - all species use the same 4 letter code* This DNA code system had to be the same since the first form of life* This implies it never changed during the proposed evolutionary period.

It is from these points that I conclude that it is very unlikely since there is nothing that prevent codes from "mutating" even the DNA code. With a medium that represents 4 digits there is quite a view different code systems that can be represented.

If I am correct then the implications should be self evident. If I am wrong then I would like to learn.

Michael: It is from these points that I conclude that it is very unlikely since there is nothing that prevent codes from "mutating" even the DNA code.

When networks of interactions evolve, certain nodes become preferentially attached. As the process continues, these nodes become more and more essential to the workings of the rest of the network. Once established, these nodes become resistant to change. That's what Crick meant by a frozen genetic code. Further optimization becomes less important as evolution proceeds through additional attachments. However, this doesn't prevent addendums to the genetic code.

Indeed, analysis indicates that the genetic code probably couldn't have evolved all at once, but evolved from a more primitive code that was then added to over time. So, the original genetic code may have been due to stereochemical affinity, was optimized to near a local fitness peak, additional assignments were made, and then more-or-less froze in place.

Michael: Do you have any proposed Darwinian reason for this "Code Freeze" to be enforced?

Changes to the genetic code are nearly always detrimental.

A more general answer was provided above. In an evolving network, some relationships become established and other relationships become dependent on those established relationships. Even if it might make sense to change those established relationships, it may require simultaneously changing many other relationships. As the network continues to evolve, these established relationships become increasingly resistant to change.

That doesn't mean they can never change, but they tend to change only tangentially. In terms of the overall network, we expect lots of small changes, a few large changes, and only the very rare revolution.

I fail to see a mechanism in your explanation above. You simply state the current state of affairs and claim it to be a mechanism.

Everyone knows that the DNA is actually part of a very complex coding machine that "protects" it from being changed. Unfortunately you cannot simply claim the entire genetic machinery to be the proof of the proposed mechanism that caused the "code freeze".

Where is the mechanism that caused the "code freeze"? I know about at least one mechanism. It is called design... Why do you object to that mechanism if you cannot present your own?

I think your reasoning proofs that there might be some very good experimental biologists, able to analyze the intricacies of biological systems. But there is very few good theoretical biologists that can theorize valid mechanisms that caused certain features.

The reason is not that they are stuck on naturalism or materialism, it is simply being stuck on Darwinism. ID is pure natural science for the simple reason that design detection happens only in the physical universe.

Your poor eyesight is not an argument, but let's look at your argument again.

Michael: * The DNA code is universal - all species use the same 4 letter code* This DNA code system had to be the same since the first form of life* This implies it never changed during the proposed evolutionary period.

The second step is incorrect. Your argument is based on a misunderstanding of evolutionary theory.

Michael: Where is the mechanism that caused the "code freeze"?

Replicating populations competing for limited resources. This can be modeled as network evolution. See above.

Your mechanism:"Replicating populations competing for limited resources. This can be modeled as network evolution. See above."

Since it is clear that you are unable to see the problem with this proposed state of affairs to be a mechanism capable of "code freeze" or any fundamental property of genes at all, I will end my effort.

P.S. You confirm that Neo Darwinism cause very strange behavior. And it is brought about by experimental biology killing the reigning theories.

Michael says: "I am very aware of the fact that it will be catastrophic for the DNA code system to change at all during the entire proposed evolutionary period. That is my argument exactly. Your objection on the one hand shows this but on the other hand you don't show me how Darwinian processes will prevent the DNA code to change at all. That is my argument, Darwinian processes will most probably change the DNA code system, not the straw man you erected."

I haven't a clue what you mean. I consider natural selection to be a Darwinian process. We seem to agree a change would be catestrophic - that means a catestrophic loss of fitness and no viable phenotype with any change.

How does this lead you to the statement that Darwinian processes "will most probably change the DNA code system"?

Michael: Since it is clear that you are unable to see the problem with this proposed state of affairs to be a mechanism capable of "code freeze" or any fundamental property of genes at all, I will end my effort.

You haven't indicated any willingness to address the answer provided. Simply waving your hands is not an argument.

"How does this lead you to the statement that Darwinian processes "will most probably change the DNA code system"?"

That is exactly what random mutations will do... changing the DNA code system, not just the messages.

If Darwinism were the processes that caused life you should actually see life forms using various code systems successfully to the same extent that you have so many different building blocks. In fact Darwinism should have achieved the same computational mechanism using a different code system, leading to the same computational outcomes. Call it fitness through multiple mutated computational mechanisms.

Why a multiple? Because that is how code systems work. You can achieve the same computational outcome using almost any valid code system.

"You haven't indicated any willingness to address the answer provided. Simply waving your hands is not an argument. "

I really tried but my bio-know-how is not up to par and therefore I asked to be enlightened by someone who can break it down in layman's terms. (I am not a biologist - information science is my field) You would see my questions remain focused pure science method, philosophy and information theory. I never pretended to know bio terms inside out.

I will consider myself disqualified to discuss the matter with you, if you prefer... but honestly... I am bored with your line of argument in general as I stated before, you just don't see the flaws of your beloved Darwinism.

Michael, do you understand the basic evolutionary mechanisms? If we have two competing strains, with different but just as efficient genetic codes, then eventually — all else equal — one strain will eventually become fixed and the other extinct. This is a simple mathematical consequence. All else is not always equal, but you might start by trying to understand this fundamental concept of genetic drift.

I have made the mistake of making comments on this subject on Dr. Hunter blog here as well as the same post on Uncommon Descent.http://www.uncommondescent.com/intelligent-design/the-code-within-the-code/#comments (mullerpr is another account name)

My comment regarding my ignorance of bio-lingo was when I thought that "the answer provided..." by you was the "stereochemical hypothesis" actually presented by Nakashima on that discussion.

I do understand your faith statements in the efficacy of "genetic drift", but you clearly cannot see how bloated and pretentious that hypothesis is. In this application you simply assume mutation and selection will only choose one DNA code system in the end. I simply challenge that state of affairs not to be consistent with random forming patterns under constant pressure from random natural interventions.

I would therefore elaborate my actual argument to abimer:

"In fact Darwinism should have achieved the same computational mechanism [...that is mechanisms that create "fit for survival" life forms] using an entirely different code system, leading to the same computational outcomes [same fitness level as current life forms]. Call it fitness through multiple mutated computational mechanisms.

You clearly did not get the consequences of my argument because you just assumed I did not have "selection" or "fit for survival" concepts in mind. I clearly had that in mind in the first place. I even gave it a name "Fitness through multiple mutated computational mechanisms"

Michael: I do understand your faith statements in the efficacy of "genetic drift", but you clearly cannot see how bloated and pretentious that hypothesis is.

Michael, you suggested that darwinism requires that multiple strains of genetic codes should be extant. That is not entailed in the theory, and there are several mechanisms that might result in a single genetic code, including selection and drift.

Michael: Fitness through multiple mutated computational mechanisms

Your statement seemed to imply multiple strains, each with a different genetic code, but equally fit. If this is correct, then please respond to this statement:

If we have two equally fit strains, then eventually — all else equal — one strain will become fixed and the other extinct. This is a simple mathematical consequence.